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IACM-Bulletin of January 12, 2014

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Uruguay — Foreign firms want to study the therapeutic potential of cannabis in the country

Foreign firms want to open laboratories in Uruguay to study the potential uses of medicinal cannabis now that the drug has been legalized in the South American country. Uruguay's Congress recently approved creation of the world's first national marketplace for legal cannabis.

Presidential Spokesman Diego Canepa said that foreign companies have told the government they'd like to set up there. Canepa is quoted by the local daily El Observador as saying that "Uruguay will become a hub for biotechnology." El Observador also says that Canada's government has started talks to import cannabis from Uruguay for medicinal purposes. Uruguay's law doesn't consider the possibility of exporting cannabis, although it could be included after a government commission rules in April.

Associated Press of 6 January 2014

Science/Animal — A natural hormone protects the brain from overactivation of the CB1 receptor by THC

Two research teams of the French institute INSERM in Bordeaux led by Pier Vincenzo Piazza and Giovanni Marsicano discovered that pregnenolone, a molecule produced by the brain, acts as a natural defence mechanism against some effects of THC in rats and mice. Pregnenolone prevents THC from fully activating the CB1 receptor that when strongly stimulated causes the intoxicating effects of cannabis. By identifying this mechanism, the INSERM teams are already developing new approaches for the treatment of cannabis addiction. These results were published in Science.

Experiments conducted in cell cultures with the human CB1 receptor on their surface confirm that pregnenolone can also counteract the molecular action of THC in humans. Pier Vincenzo Piazza explains that "pregnenolone cannot be used as a treatment because it is badly absorbed when administered orally and once in the blood stream it is rapidly transformed in other steroids." However, the researcher says that there is strong hope of seeing a new addiction therapy emerge from this discovery. "We have now developed derivatives of pregnenolone that are well absorbed and stable. (…) We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence."

Vallée M, et al. Science. 2014;343(6166):94-8.

Molecule Discovered That Protects Brain from Cannabis Intoxication.

USA — World's first state-licensed cannabis retailers open doors in Colorado

The world's first state-licensed cannabis retailers legally permitted to sell cannabis for recreational use opened for business in Colorado on 1 January with long lines of customers, marking a new chapter in America's drug culture. Roughly three dozen former medical cannabis dispensaries newly cleared by state regulators to sell cannabis to consumers interested in nothing more than its mind- and mood-altering properties began welcoming customers.

Hundreds of patrons, some from distant states and many huddling outside in the bitter cold and snow for hours, cued up to be among the first buyers. The highly-anticipated New Year's Day opening launched an unprecedented commercial cannabis market that Colorado officials expect will ultimately gross 578 million dollars in annual revenues, including 67 million dollars in tax receipts for the state.

Reuters of 1 January 2014

News in brief

USA — 55 per cent support legalization of cannabis

Another poll indicates a majority of Americans now support legalizing cannabis, a sharp turnaround from past decades. The poll conducted by CNN and ORC International indicates 55 per cent of respondents said the drug should be legalized; 44 per cent said it should not. The findings, CNN said, mirror a Gallup poll released in October that showed similar rates of response in favor of legalizing cannabis.

UPI of 7 January 2014

Germany/Holland — Dutch clampdown drives cannabis farms to Germany

Large cannabis plantations are popping up more frequently in Germany's sparsely populated north east. A crackdown in the Netherlands has pushed up production of the drug. Since 2011, police have uncovered around 50 cannabis farms in empty buildings across the north-eastern state of Mecklenburg Western-Pomerania. Before this they would find only a couple each year. Dutch authorities have been coming down hard on cannabis growers since 2011, according to Mecklenburg Western-Pomerania's office for criminal investigation (LKA), which published the figures.

The Local of 2 January 2014

Science/Human — Sativex effective as monotherapy in spasticity in MS

Over a 15-month timeframe, 120 patients with spasticity due to multiple sclerosis received the cannabis extract Sativex (THC:CBD spray). Sativex was used as add-on therapy in 95 patients and as monotherapy in 25 patients to achieve best-possible therapeutic results. The mean spasticity 0-10 numerical rating scale (NRS) score decreased by 57%, from 7.0 before treatment to 3.0 within 10 days of starting THC:CBD spray. The mean dosage was 4 sprays/day. Authors wrote that the medication “was effective and well tolerated as add-on therapy or as monotherapy in a relevant proportion of patients with resistant MS spasticity.”

Marianne Strauss Klinik, Berg, Germany.

Koehler J, et al. Int J Neurosci. 2014 Jan 6. [in press]

Science/Human — Severity of MS associated with a certain variant of the CB1 receptor

Researchers found that multiple sclerosis patients with certain variants of the CB1 receptor had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. They wrote that their “results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS.”

Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy.

Rossi S, et al. PLoS One 2013;8(12):e82848.

Science/Human — Changes of the endocannabinoid system associated with irritable bowel syndrome

Endocannabinoid and endocannabinoid-like fatty acid amide levels in blood plasma correlate with pain-related symptoms in patients with irritable bowel syndrome (IBS) suffering from diarrhoea or constipation. Patients with IBS and diarrhoea had higher levels of 2-AG and lower levels of oleoylethanolamide and palmitoylethanolamide. In contrast, patients with constipation had higher levels of oleoylethanolamide. Researchers concluded that the “here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.”

Snyder Institute for Chronic Diseases, University of Calgary, Canada.

Fichna J, et al. PLoS One. 2013;8(12):e85073.

Science/Animal — CBD inhibited cancer of the colon

Both a cannabis extract rich in CBD and pure CBD reduced cell proliferation in tumour cells, but not in healthy colon cells. The effect of the extract was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. Researcher concluded that CBD-rich cannabis extracts “attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation.”

Department of Pharmacy, University of Naples Federico II, Italy.

Romano B, et al. Phytomedicine. 2013 Dec 24. [in press]

Science/Animal — The endocannabinoid system is altered in epilepsy

The concentration of anandamide (AEA) in cerebrospinal fluid (CSF) of epileptic dogs was higher than in CSF of healthy dogs. Dogs with cluster seizures and/or status epilepticus and with seizure activity for more than six months displayed the highest endocannabinoid concentrations. Authors wrote that their results confirm the hypothesis that the endocannabinoid system is altered in epilepsy of dogs.

Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany.

Gesell FK, et al. BMC Vet Res 2013;9(1):262.